In the Journals

Five major psychiatric disorders may share common genetic risk factors

Autism spectrum disorder, attention-deficit/hyperactivity disorder, bipolar disorder, major depressive disorder and schizophrenia all share common genetic risk factors, according to the results of the largest genetic study of psychiatric disorders to date.

“This study indicates that some specific genetic variants confer risk to a range of psychiatric disorders that are treated as clinically distinct,” study researcher Jordan Smoller, MD, of Massachusetts General Hospital in Boston, told Psychiatric Annals. “The findings also highlight the role of calcium channel genes, which may provide a treatment target that is relevant to a range of psychiatric disorders.” 

Jordan Smoller, MD 

Jordan Smoller

Smoller and colleagues from the Psychiatric Genomics Consortium studied genome-wide single-nucleotide polymorphism (SNP) data of the five disorders in 33,332 patients and 27,888 individuals in a control group of European ancestry.

Specifically, the researchers found that SNPs at four loci on the chromosomes 3p21 and 10q24, and SNPs in the two genes CACNA1C and CACNB2, were associated with all five disorders. CACNA1C, which has been linked to bipolar disorder, major depressive disorder and schizophrenia in previous genetic studies, and CACNB2 both help regulate calcium in brain cells.

The combined polygenetic risk scores confirmed cross-disorder effects, especially among the adult-onset disorders: bipolar disorder, major depressive disorder and schizophrenia. Additional analyses indicated that genes associated with calcium channel signaling play a role in the five disorders.

Smoller and colleagues noted that the findings coincide with the revision of the DSM-5, set to be published in May, which has spurred debate recently over diagnostic boundaries between psychiatric disorders.

“Significant progress has been made in understanding the genetic risk factors underlying psychiatric disorders,” Smoller said. “Our results provide new evidence that may inform a move beyond descriptive syndromes in psychiatry and towards classification based on underlying causes.”

In an accompanying editorial, Italian researchers Alessandro Serretti, MD, and ChiaraFabbri, MD, of the department of biomedical and neuromotor sciences at the University of Bologna, said progress has been made using full-genome sequencing and analysis, which may lead to better identification of psychiatric disorders and treatment options.

“We therefore believe that genetics, possibly thanks to more comprehensive phenotype and endophenotype assessments, can contribute to prediction and prevention of psychiatric diseases, along with the identification of molecular targets for new generations of psychotropic drugs,” they said.

For more information:

Serretti A. Lancet. 2013;doi:10.1016/S0140-6736(13)602223-8.

Smoller J. Lancet. 2013;doi:10.1016/S0140-6736(12)62129-1.

Disclosure: The researchers report no relevant financial disclosures.

Autism spectrum disorder, attention-deficit/hyperactivity disorder, bipolar disorder, major depressive disorder and schizophrenia all share common genetic risk factors, according to the results of the largest genetic study of psychiatric disorders to date.

“This study indicates that some specific genetic variants confer risk to a range of psychiatric disorders that are treated as clinically distinct,” study researcher Jordan Smoller, MD, of Massachusetts General Hospital in Boston, told Psychiatric Annals. “The findings also highlight the role of calcium channel genes, which may provide a treatment target that is relevant to a range of psychiatric disorders.” 

Jordan Smoller, MD 

Jordan Smoller

Smoller and colleagues from the Psychiatric Genomics Consortium studied genome-wide single-nucleotide polymorphism (SNP) data of the five disorders in 33,332 patients and 27,888 individuals in a control group of European ancestry.

Specifically, the researchers found that SNPs at four loci on the chromosomes 3p21 and 10q24, and SNPs in the two genes CACNA1C and CACNB2, were associated with all five disorders. CACNA1C, which has been linked to bipolar disorder, major depressive disorder and schizophrenia in previous genetic studies, and CACNB2 both help regulate calcium in brain cells.

The combined polygenetic risk scores confirmed cross-disorder effects, especially among the adult-onset disorders: bipolar disorder, major depressive disorder and schizophrenia. Additional analyses indicated that genes associated with calcium channel signaling play a role in the five disorders.

Smoller and colleagues noted that the findings coincide with the revision of the DSM-5, set to be published in May, which has spurred debate recently over diagnostic boundaries between psychiatric disorders.

“Significant progress has been made in understanding the genetic risk factors underlying psychiatric disorders,” Smoller said. “Our results provide new evidence that may inform a move beyond descriptive syndromes in psychiatry and towards classification based on underlying causes.”

In an accompanying editorial, Italian researchers Alessandro Serretti, MD, and ChiaraFabbri, MD, of the department of biomedical and neuromotor sciences at the University of Bologna, said progress has been made using full-genome sequencing and analysis, which may lead to better identification of psychiatric disorders and treatment options.

“We therefore believe that genetics, possibly thanks to more comprehensive phenotype and endophenotype assessments, can contribute to prediction and prevention of psychiatric diseases, along with the identification of molecular targets for new generations of psychotropic drugs,” they said.

For more information:

Serretti A. Lancet. 2013;doi:10.1016/S0140-6736(13)602223-8.

Smoller J. Lancet. 2013;doi:10.1016/S0140-6736(12)62129-1.

Disclosure: The researchers report no relevant financial disclosures.